Protein Kinase C Pathway Is Involved in Regulating the Secretion of Prostatic Acid Phosphatase in Human Prostate Cancer Cells

Lin, Ming Fong; Zhang, Xiu Qing; Dean, Jeanenne; Lin, Fen Fen

doi:10.1006/cbir.2001.0794

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…In prostate cancer cells, Ca v 3.2 mediates Ca 2+ -dependent secretion, e.g. release of potential mitogenic factors such as neurotensin and PTHrP [28,44] that are upregulated during neuroendocrine-like differentiation (see Fig. 1L, M), in agreement with the previous reports [45,46].…”

Section: Discussionsupporting

confidence: 91%

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

Fukami

Sekiguchi

Asano

et al. 2015

Biochemical Pharmacology

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Section: Discussionsupporting

confidence: 91%

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

Fukami

Sekiguchi

Asano

et al. 2015

Biochemical Pharmacology

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“…PAP is one of the main secretory products released by prostate cells with prostate-specific antigen (PSA) and was shown to exist in two forms, an intracellular (cPAP) and a secreted one (sPAP), the latter being localized in secretory granules of prostate cells (for review, see Ref. 33) and released upon stimuli like protein kinase C activation in LNCaP cells (25). Until now, it was yet to be shown that its secretion is finely regulated by calcium.…”

Section: Discussionmentioning

confidence: 99%

“…In prostate cells the L(ϩ)-tartrate-sensitive acid phosphatase activity has conventionally been used to represent PAP activity (25).…”

mentioning

confidence: 99%

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

Gackière

Bidaux

Delcourt

et al. 2008

Journal of Biological Chemistry

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Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgenindependent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.Prostate cancer is, in its early stages, an androgen-dependent pathology, meaning that its progression relies on the presence of active steroid male hormones. Treatments developed for many years have been based on this characteristic feature of prostate cancer and, thus, aimed at decreasing the plasma concentration of testosterone or dihydrotestosterone, the prostate active androgen. Although these treatments are particularly valuable in the early development of the disease, leading to the regression of cancers, about a third of the patients suffer a relapse after a few years of hormone therapy. At this stage of hormone refractory disease, deprivation of androgens has no further incidence on the growth of the prostate cancer, and no curative therapy is currently effective (for review, see Ref. 1).The androgen-independent stage of prostate cancer has been shown to be associated with, among others, the development of neuroendocrine differentiation (2). These neuroendocrine features include the appearance of neuroendocrine cell foci surrounded by proliferating epithelial cells (3). Because neuroendocrine prostate cells in normal, hyperplastic, or cancerous tissue secrete many neuropeptides with mitogenic activities like parathyroid hormone-related peptide, calcitonin, or gastrin-related peptides, it has been proposed that paracrine secretion of neurosecretory products released by neuroendocrine cells could be responsible for the progression of cancer toward an androgen-independent stage (for review, see Ref. 4). Indeed, it has been shown for instance that the expression of neuroendocrine markers like chromogranin A is correlated with tumor dedifferentiation (5) and that the presence of neuroendo...

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“…In brief, PKC was partially purified by a DEAE‐cellulose column and its activity was quantified in the presence or absence of a specific inhibitor of PKC. The inhibitor‐sensitive protein kinase activity was used to represent the specific PKC activity (Lin et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

Activation of PKC‐ε and ERK1/2 participates in shear‐induced endothelial MCP‐1 expression that is repressed by nitric oxide

Wang

Lien

Cheng

et al. 2003

Journal Cellular Physiology

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Vascular endothelial cells (ECs) continuously experience hemodynamic shear stress generated from blood flow. Previous studies have demonstrated that shear stress modulates monocyte chemotactic protein-1 (MCP-1) expression in ECs. This study explored the roles of protein kinase C (PKC), extracellular signal-regulated protein kinase (ERK1/2), and nitric oxide (NO) in sheared-induced MCP-1 expression in ECs. The activation of PKC-alpha and PKC-epsilon isoforms was observed in ECs exposed to shear stress. The use of an inhibitor (calphostin C) to PKC-alpha and PKC-epsilon decreased ERK1/2 activation and MCP-1 induction by shear, whereas an inhibitor (Go6976) to PKC-alpha did not affect ERK1/2 activation or MCP-1 induction. Inhibition of ERK1/2 activation by PD98059 blocked MCP-1 induction. Transfection of ECs with an antisense to PKC-epsilon abolished the shear inducibility of MCP-1 promoter. These results demonstrate that PKC-epsilon and ERK1/2 participate in shear-induced MCP-1 expression. We also examined the regulatory role of NO in MCP-1 expression. An NO donor (NOC18) suppressed shear-induced activation of PKC-epsilon and ERK1/2, and also repressed MCP-1 induction. Consistently, overexpression of endothelial nitric oxide synthase (eNOS) to enhance the endogenous generation of NO in ECs decreased the activation of PKC-epsilon and ERK1/2, and also inhibited MCP-1 expression. Taken together, these findings suggest that PKC-epsilon and ERK1/2 are critical in the signaling pathway(s) leading to the MCP-1 expression induced by shear stress. Additionally, this study indicates that NO, by repressing PKC-epsilon activity and ERK pathway activation, attenuates shear-induced MCP-1 expression.

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Protein Kinase C Pathway Is Involved in Regulating the Secretion of Prostatic Acid Phosphatase in Human Prostate Cancer Cells

Cited by 9 publications

References 43 publications

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells

CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells

Activation of PKC‐ε and ERK1/2 participates in shear‐induced endothelial MCP‐1 expression that is repressed by nitric oxide

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